Elsevier

Biological Psychiatry

Volume 84, Issue 9, 1 November 2018, Pages 644-654
Biological Psychiatry

Archival Report
Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium

https://doi.org/10.1016/j.biopsych.2018.04.023Get rights and content
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open access

Abstract

Background

The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group.

Methods

The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11–78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10–87 years; 53% male) assessed with standardized methods at 39 centers worldwide.

Results

Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen’s d = −0.530/−0.516) and smaller surface area (left/right hemisphere: Cohen’s d = −0.251/−0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset.

Conclusions

The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.

Keywords

Cortical
Imaging
Meta-analysis
Schizophrenia
Surface area
Thickness

Cited by (0)

Members of the Karolinska Schizophrenia Project: Lars Farde (Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm County Council, Stockholm, Sweden), Lena Flyckt (Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm County Council, Stockholm, Sweden), Göran Engberg (Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden), Sophie Erhardt (Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden), Helena Fatouros-Bergman (Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm County Council, Stockholm, Sweden), Simon Cervenka (Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm County Council, Stockholm, Sweden), Lilly Schwieler (Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden), Fredrik Piehl (Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden), Ingrid Agartz (Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm County Council, Stockholm, Sweden; NORMENT, K.G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, University of Oslo; Department of Psychiatry Research, Diakonhjemmet Hospital, Oslo, Norway), Karin Collste (Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm County Council, Stockholm, Sweden), Pauliina Victorsson (Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm County Council, Stockholm, Sweden), Anna Malmqvist (Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden), Mikael Hedberg (Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden), and Funda Orhan (Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden).